Molecular bases of Sorcin-dependent resistance to chemotherapeutic agents

Genovese, Ilaria; Ilari, Andrea; Battista, Theo; Chiarini, Valerio; Fazi, Francesco; Fiorillo, Annarita; Colotti, Gianni

doi:10.20517/cdr.2018.10

Cited by 3 publications

(4 citation statements)

References 130 publications

(197 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…At least four different Sorcin isoforms are transcribed in human, i.e., isoforms A (a 15 kb-transcript, with 8 exons and 7 introns, translated into a 22-kDa, 198-residues long isoform), B, C, and D (translated into shorter, 19-kDa, isoforms, lacking part of the N-terminal domain and/or the last amino acids of the C-terminal domain); the 22-kDa isoform A is the most studied sorcin isoform, although some studies refer to 19-kDa forms of the protein. A sorcin-like pseudogene (SRIL) is located in chromosome 4 [2].…”

Section: Sorcin Structure and Calcium-dependent Activationmentioning

confidence: 99%

See 1 more Smart Citation

Roles of Sorcin in Drug Resistance in Cancer: One Protein, Many Mechanisms, for a Novel Potential Anticancer Drug Target

Battista

Fiorillo

Chiarini

et al. 2020

Cancers

Self Cite

View full text Add to dashboard Cite

The development of drug resistance is one of the main causes of failure in anti-cancer treatments. Tumor cells adopt many strategies to counteract the action of chemotherapeutic agents, e.g., enhanced DNA damage repair, inactivation of apoptotic pathways, alteration of drug targets, drug inactivation, and overexpression of ABC (Adenosine triphosphate-binding cassette, or ATP-binding cassette) transporters. These are broad substrate-specificity ATP-dependent efflux pumps able to export toxins or drugs out of cells; for instance, ABCB1 (MDR1, or P-glycoprotein 1), overexpressed in most cancer cells, confers them multidrug resistance (MDR). The gene coding for sorcin (SOluble Resistance-related Calcium-binding proteIN) is highly conserved among mammals and is located in the same chromosomal locus and amplicon as the ABC transporters ABCB1 and ABCB4, both in human and rodent genomes (two variants of ABCB1, i.e., ABCB1a and ABCB1b, are in rodent amplicon). Sorcin was initially characterized as a soluble protein overexpressed in multidrug (MD) resistant cells and named “resistance-related” because of its co-amplification with ABCB1. Although for years sorcin overexpression was thought to be only a by-product of the co-amplification with ABC transporter genes, many papers have recently demonstrated that sorcin plays an important part in MDR, indicating a possible role of sorcin as an oncoprotein. The present review illustrates sorcin roles in the generation of MDR via many mechanisms and points to sorcin as a novel potential target of different anticancer molecules.

show abstract

Section: Sorcin Structure and Calcium-dependent Activationmentioning

confidence: 99%

“…(MDR). In fact, sorcin is overexpressed in many human cancers, as lymphomas, leukemias, gastric, breast, lung, nasopharyngeal, ovarian tumors, adenocarcinoma, glioblastoma, astrocytoma, oligodendroglioma, and multidrug (MD)-resistant tumors, with respect to normal tissues (for a review, [1,2]).…”

Section: Introductionmentioning

confidence: 99%

Roles of Sorcin in Drug Resistance in Cancer: One Protein, Many Mechanisms, for a Novel Potential Anticancer Drug Target

Battista

Fiorillo

Chiarini

et al. 2020

Cancers

Self Cite

View full text Add to dashboard Cite

show abstract

“…Many actors play a role in these processes. Signal transduction via Ca 2+ /calmodulin is linked to numerous major ER Ca 2+ load, participates in preventing ER stress and the unfolded protein response; iv) interacts in a calciumdependent fashion with αSyn, presenilin2 (PS2) and other proteins, and regulates PS2 58,59 ; for these reasons, Sorcin may represent a useful marker and an important player in the mechanisms of neurodegeneration.…”

Section: Discussionmentioning

confidence: 99%

Sorcin is an early marker of neurodegeneration, Ca2+ dysregulation and endoplasmic reticulum stress associated to neurodegenerative diseases

et al. 2020

Self Cite

View full text Add to dashboard Cite

Dysregulation of calcium signaling is emerging as a key feature in the pathogenesis of neurodegenerative diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and Huntington’s disease (HD), and targeting this process may be therapeutically beneficial. Under this perspective, it is important to study proteins that regulate calcium homeostasis in the cell. Sorcin is one of the most expressed calcium-binding proteins in the human brain; its overexpression increases endoplasmic reticulum (ER) calcium concentration and decreases ER stress in the heart and in other cellular types. Sorcin has been hypothesized to be involved in neurodegenerative diseases, since it may counteract the increased cytosolic calcium levels associated with neurodegeneration. In the present work, we show that Sorcin expression levels are strongly increased in cellular, animal, and human models of AD, PD, and HD, vs. normal cells. Sorcin partially colocalizes with RyRs in neurons and microglia cells; functional experiments with microsomes containing high amounts of RyR2 and RyR3, respectively, show that Sorcin is able to regulate these ER calcium channels. The molecular basis of the interaction of Sorcin with RyR2 and RyR3 is demonstrated by SPR. Sorcin also interacts with other ER proteins as SERCA2 and Sigma-1 receptor in a calcium-dependent fashion. We also show that Sorcin regulates ER calcium transients: Sorcin increases the velocity of ER calcium uptake (increasing SERCA activity). The data presented here demonstrate that Sorcin may represent both a novel early marker of neurodegenerative diseases and a response to cellular stress dependent on neurodegeneration.

show abstract

“…Sorcin is one of the most highly expressed calcium-binding proteins. It is an oncoprotein, which is co-amplified with the efflux pump, ABCB1, in multidrug-resistant cells [ 174 ] . Overexpression of Sorcin is found in many tumors resistant to taxanes and vinca alkaloids and inversely correlates with response and outcome of chemotherapy [ 175 ] .…”

Section: Drug Resistancementioning

confidence: 99%